Cycloaddition of norbornadiene

Cycloaddition of norbornadiene with allene takes place to yield the cyclobutene derivative 10[5], Cyclodimerization of 1,2-cyclononadiene (11) affords a mixture of stereoisomers of the cyclobutane derivatives 12[6,7],... 

The cycloaddition between norbornadiene (23 in Scheme 1.12) and maleic anhydride was the first example of a /mmo-Diels-Alder reaction [55]. Other venerable examples are reported in Scheme 1.12 [56]. Under thermal conditions, the reaction is generally poorly diastereoselective and occurs in low yield, and therefore several research groups have studied the utility of transition metal catalysts [57]. Tautens and coworkers [57c] investigated the cycloaddition of norbornadiene and some of its monosubstituted derivatives with electron-deficient dienophiles in the presence of nickel-cyclo-octadiene Ni(COD)2 and PPhs. Some results are illustrated in Tables 1.4 and 1.5. 

A cobalt-based catalyst, prepared by reducing Co(acac)3 with diethylalumi-num chloride in the presence of the bidentate ligand l,2-bis(triphenylphosphi-no)ethane, accelerates [87] the cycloadditions of norbornadiene (88) with a variety of acetylenes (Equation 3.30). 

Lewis-acid catalysis is effective in intermolecular as well as intramolecular /zomo-Diels-Alder reactions. Thus, complex polycyclic compounds 93 have been obtained in good yield by the cycloaddition of norbornadiene-derived dienynes 92 by using cobalt catalyst, whereas no reaction occurred under thermal conditions [91] (Scheme 3.18). 

Table 2.16 1,3-Dipolar cycloaddition of norbornadiene-tethered nitrones...

The intramolecular 2 - - 2 - - 1-cycloadditions of allene, alkyne (106), and carbon monoxide yield a -methylene-(107) or 4-alkylidene-cyclopentenones (108) depending on the allene structure or the reaction conditions (Scheme 4i).i59.i6o The cobalt-catalysed 4 - - 2 - - 2-cycloaddition of norbornadienes (109) with buta-1,3-dienes readily produces cycloadducts (110) when a bimetal system is used (Scheme A2) ... 

Titanacycle 10 ring-opens photochemically at temperatures well below 0°C, Eq. (27) [41]. The unstable titanium carbene 20 can be trapped by exo-trans-exodiene 21, derived from (2 + 2) cycloaddition of norbornadiene, to produce a mixture of two isomeric bis(titanacyclobutanes), 22a, b [42]. Bis(titanacycle) 22a, b could not be synthesized cleanly by thermolysis of 10 because formation of 22a, b competes with ring-opening and the addition of a second equivalent of diolefin. 

Enantioselective homo-Diels-Alder cycloaddition can also be achieved with Co(II)/Zn catalysts chirally modified with amino acid derived phosphite ligands63, Stereoselective cycloaddition of norbornadiene has also been observed with enones64 to give the [2 + 2 + 2] adducts, while with dienes in the presence of chirally modified Co(II)/Et2AlCl catalysts optically active [4 + 2 + 2] adducts were obtained in up to 66% yield and 79% ee65. 

Tam and co-workers reported highly regio- and stereoselective intramolecular 1,3-dipolar cycloaddition of norbornadiene-tethered nitrile oxide 295 for the construction of isoxazoUne rings 296 fused to bicycUc framework... 

Only a few reactions of benzodithiadiazines have been investigated. In common with dithiatriazines 12.8, the anti-aromatic system 12.12 (R = H) undergoes a reversible 5,5 -cycloaddition with norbornadiene. The reaction of 12.12 (R = F) with triphenylphosphine results in a ring contraction to give the imino 2 -phosphane 12.13. ... 

Norbornadienes, norbornenones and their homologs have been prepared [23, 24] by cycloaddition of cyclopentadiene (21) and cyclohexadiene (22) with l-benzenesulfonyl-2-trimethylsilylacetylene (23) and l-ethoxy-2-carbomethox-yacetylene (24). Both were efficient dienophiles in the cycloaddition processes and dienophile 23 acted as an effective acetylene equivalent (Scheme 2.12). Norbornanes and their homologs can also be attained by Diels-Alder reaction... 

The /lomo-Diels-Alder reaction is a [2 + 2 + 2] cycloaddition of a 1,4-diene with a dienophile which produces two new bonds and a cyclopropane ring. This reaction is an example of a multi-ring-forming reaction that to date has found few applications in synthesis, since the use of 1,4-dienes has been limited mainly to bridged cyclohexa-1,4-dienes and almost exclusively to norbornadiene. Lewis-acid catalysts accelerate /lowo-Diels-Alder reactions and increase the selectivity for the [2 + 2 + 2] vs. [2 + 2] cycloaddition. 

Cycloaddition of bicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic anhydride 81 with cyclopentadiene was also studied by Bartlett et al., who found exclusive top addition, the top-endo/top-exo ratio being 3 2 [147]. The endolexo ratio is significantly different from that of 80 (60-70 1). The observed top selectivity in norbornadiene (80) and norbomene (81) derivatives is consistent with the inherent top reactivity of norbomanone 25 and norbomene 57. Orbital unsymmetrization of the dienophile... 

The intramolecular cycloaddition of the norbornadiene-tethered nitrile oxides 110 (Eq. 11 and Table 11) was reported to be highly regio- and stereoselective, providing the exo cycloadduct 111 as the exclusive product out of the four possible regio/stereoisomers [36]. The cycloadduct 111 provides a stereoselective entry into tricyclic (e.g., 112) and spirocyclic (e.g., 113) frameworks. 

Pyrazoles can be synthesized by thermal cycloreversion of adducts formed in the 1,3-dipolar cycloaddition of alkyldiazoacetates with norbornadiene. The rate of the primary process of cycloaddition is accelerated by iron pentacarbonyl (Scheme 88)155 a similar catalytic effect has been observed during the formation of ethyl 5-phenyl-A2-pyrazoline-3-carboxylate from cycloaddition of ethyl diazoacetate and styrene.155 Reactions of this type are catalyzed presumably because of coordination of one or both reactants to the transition metal, and a wider study of the effect of a variety of complexes on 1,3-dipolar cycloaddition processes would be valuable. 

Bistrifluoromethyl-l,3,4-thiadiazole 71 undergoes a Diels-Alder reaction with norbornadiene under high pressure to give the unstable cycloadduct 72 which rapidly loses dinitrogen forming the 1,3-dipolar intermediate 73. The [4+2] cycloaddition of the intermediate 73 with a second alkene affords product 74 in 29% yield (Scheme 5) <1997SL196>. 

Like the cyclization of the parent system, the photocyclization of hetero analogues of norbornadiene was reported many years ago. Recent interest in this area will serve to illustrate the potential of the conversions. Thus the irradiation of the oxanorbomadiene system 259 brings about conversion to the oxepine 260138. The formation of 260 presumably arises by quadricyclane 261 formation, followed by secondary photolytic ring-opening. Other research has shown that irradiation of the oxanorbomadiene 262 follows the same reaction mode and it undergoes (2 + 2)-cycloaddition to the quadricyclane derivative 263. Apparently, in this instance, cycloreversion affords the ylide 264 that can be trapped by suitable addends, giving the adducts illustrated in Scheme 3139. 

The final example of the intramolecular 1,3-dipolar cycloadditions of nitrile oxides is the formation of the norbornadiene-derived tetracyclic adducts 146, described by Tam and co-workers (240,241). The nitrile oxide 145, formed from 144 by dehydration, can in principle give rise to four different cycloaddition products (three [2,3]-cycloaddition products). In practice, only diastereomer 146 was obtained. The reaction was used on substrates with a variety of different substituents (R=H, Me, hexyl. Cl, Br, C02Me, CH20Me), and in these cases, yields ranging between 66-89% were obtained (Scheme 12.48). 

Methylene-l-cyclopentenes.1 All attempts to effect cycloaddition of the acetate 1 (9,454 11,578) to alkynes are unsuccessful, but 1 does add to norbornadienes (prepared from alkynes) in the presence of a palladium(O) catalyst to form adducts that afford 4-methylene-1-cyclopentenes on flash vacuum thermolysis (equation I). 

Many pericyclic reactions take place photochemically, that is, by irradiation with ultraviolet light. One example is the conversion of norbornadiene to quadricyclene, described in Section 13-3D. This reaction would have an unfavorable suprafacial [2 + 2] mechanism if it were attempted by simple heating. Furthermore, the thermodynamics favor ring opening rather than ring closure. However, quadricyclene can be isolated, even if it is highly strained, because to reopen the ring thermally involves the reverse of some unfavorable [2 + 2] cycloaddition mechanism. 

Palladium catalyzed cyclization of l-iodo-2-((propa-l,2-dienyloxy)methyl)benzene 150 occurs with concomitant anion incorporation to furnish 4-substituted-l//-isochromenes 151 (Scheme 49) <1998TL435, 2000J(P1)3799>. In the presence of norbornadiene 152, the initially formed azide can undergo a further 1,3-dipolar cycloaddition reaction and fragmentation to give l-((l//-isochromen-4-yl)methyl)-l//-l,2,3-triazole 153 (Scheme 49) <1998TL435, 2001T7729>. 

Cycloaddition reactions of norbornadiene and its derivatives to give heterocyclic systems 92MI25. 

One of the first examples of ruthenium-catalyzed C-C bond formation afforded the synthesis of cyclobutenes, from norbornene derivatives with dimethyl acetylenedicarboxylate, and was reported by Mitsudo and coworkers [45, 46] by using various catalysts such as RuH2(CO)[P(p-C6H4F)3]3 or RuH2(PPh3)4. More recently, the complex Cp RuCl(COD) has shown to be an excellent catalyst for the [2+2] cycloaddition of norbornenes with various internal alkynes [45] (Eq. 33) and with a variety of substituted norbornenes and norbornadienes [47]. The ruthenacycle intermediate, formed by oxidative coupling, cannot undergo /1-hydride elimination and leads to cyclobutene via a reductive elimination. 

Cycloaddition reactions of a,/3-unsaturated chromium and tungsten complexes have been studied to a great extent and have been reviewed.3 -6 Our report on cycloaddition of (l-alkynyl)carbene complexes is restricted to a short abstract and an update including more recent results. A most remarkable feature of [4+2] cycloadditions of 1,3 dienes to C=C bonds of (l-alkynyl)carbene complexes, e.g., li, is that such reactions proceed under very mild conditions, compared to those for reactions of propargylic esters, e.g., 41. Thus, formation of a Diels-Alder adduct, e.g., a norbornadiene derivative 42, can be achieved at 25°C via carbene complexes instead of at 190°C via the direct route (Scheme 15).68 Ligand disengagement from compound 40 can be achieved in various ways, e.g., by formation of an ester 43 through oxidation of the Cr=C bond, or by formation of an allyl silane 4369 or a stannane.70 71... 

Benzo[ ]furan-based azide was also reported to undergo a 1,3-dipolar cycloaddition with norbornadiene as dipolar-ophile to give a triazole after extrusion of cyclopentadiene (Equation 180) <2001T7729>. 

The reaction of norbornadiene with diethyl diazenedicarboxylate affords a mixture of two 1 1 adducts 2 and 3 in approximately equal amounts25 one of the adducts 3 is produced by homo-Diels-Alder cycloaddition, as demonstrated by further conversion to quadricyclene, and the other is the oxadiazine 2, not previously identified. 

Schrauzer et al. reported a Second [2- -2- -2- -2] cycloaddition process involving the dimerization of norbornadiene to Binor-S (55) 38). 

Intermediate metallacyclopentanes are also implicated in transition metal-catalyzed alkene cycloadditions to form cyclobutanes and the corresponding cycloreversions, e.g. dimerization of norbornadiene (73JA597) and rearrangements of cubane and other cyclo-butanoid hydrocarbons (78JA2573). 

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